JP2001172218A - Method for producing ketone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrially suitable method for producing a ketone by which the ketone can be produced in high yield from a β-ketoester under a mild condition without requiring a complex operation. SOLUTION: This method for producing the ketone represented by general formula (2) [wherein, R1 is an alkyl, a cycloalkyl, an aralkyl or an aryl, (having a substituent); and R2 and R3 are H, or an alkyl, a cycloalkyl, an aralkyl or an aryl the same as or different from each other, (having a substituent)] comprises reacting the β-ketoester represented by general formula (1) [wherein, R1 to R3 have the same meanings mentioned before; and R4 is an alkyl, a cycloalkyl, an aralkyl or an aryl, (having a substituent)] with hydrogen peroxide in the presence of a base.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing ketone by decarboxylation of β-ketoester. Ketones are compounds useful as synthetic intermediates or raw materials for pharmaceuticals, agricultural chemicals, and the like.

[0002]

2. Description of the Related Art Conventionally, as a method for producing a ketone by decarboxylation of a β-keto ester, for example, a method using sodium chloride in a mixed solvent of water and dimethyl sulfoxide (Tetrahedron Lett., 1974 , 1091) or water Although the method (Org. Synth., 45, 25 (1965)) is disclosed in a solvent, there is a problem that an extremely high reaction temperature is required in each case. Although a method (Chem. Ind., 1979 , 610) in the presence of hydrochloric acid or sodium cyanide is disclosed, it is disadvantageous as an industrial production method, such as complicated handling and post-treatment.

[0003]

The object of the present invention is to solve the above-mentioned problems and to produce ketones from β-ketoesters in a high yield without the need for complicated operations under mild conditions. The present invention provides an industrially suitable method for producing ketones.

[0004]

The object of the present invention is to provide a compound of the formula (1) in the presence of a base.

[0005]

Embedded image (Wherein, R ¹ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group which may have a substituent. R ² and R ³ may be the same or different;
It represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group which may have a substituent.
R ¹ , R ² and R ³ may be bonded to each other to form a ring, or may contain a hetero atom in the ring.
R ⁴ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group which may have a substituent. )

Wherein β-ketoester represented by the following formula is reacted with hydrogen peroxide:

[0007]

Embedded image (In the formula, R ¹ , R ² and R ³ are as defined above.)

The problem is solved by the method for producing ketones shown in the above.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The starting β-ketoester used in the reaction of the present invention is represented by the aforementioned general formula (1). In the general formula (1), R ¹ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group which may have a substituent.

The alkyl group is preferably a compound having 1 to 1 carbon atoms.
10 alkyl groups are preferred, for example, methyl, ethyl, propyl (and its isomers), butyl (and its isomers), pentyl (and its isomers), hexyl (and its isomers) , A heptyl group (and its isomers), an octyl group (and its isomers), a nonyl group (and its isomers), and a decyl group (and its isomers).

The cycloalkyl group is particularly preferably an alkenyl group having 3 to 7 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and a cycloheptyl group.

The aralkyl group is preferably a group having 7 carbon atoms.
The aralkyl group of 10 to 10 is preferable, and examples thereof include a benzyl group, a phenethyl group (and its isomer), a phenylpropyl group (and its isomer), and a phenylbutyl group (and its isomer).

The aryl group is preferably a compound having 6 to 6 carbon atoms.
Preferred are 14 aryl groups, for example, a phenyl group, a naphthyl group, and an anthranyl group.

The above-mentioned alkyl group, cycloalkyl group, aralkyl group or aryl group may have a substituent. Examples of the substituent include a substituent formed through a carbon atom, a substituent formed through an oxygen atom, a substituent formed through a nitrogen atom, and at least one substituent selected from a halogen atom.

Examples of the substituent formed through the carbon atom include an alkyl group such as a methyl group, an ethyl group, a propyl group and a butyl group; an aralkyl group such as a benzyl group; an alkenyl group such as an ethenyl group; and an alkynyl group such as an ethynyl group. Groups; aryl groups such as phenyl groups; cyano groups; carboxyl groups

The substituents formed through the oxygen atom include alkoxy groups such as methoxy group, ethoxy group, propoxy group, butoxy group and benzyloxy group; aryloxy groups such as phenoxy group; acetyloxy group and benzoyloxy group. And the like.

The substituents formed through the nitrogen include:
A nitro group; an amino group.

As the halogen atom, a fluorine atom,
Examples include a chlorine atom, a bromine atom and an iodine atom.

In the above formula (1), R ² and R ³ may be the same or different, and may be a hydrogen atom, which may have a substituent, an alkyl group, a cycloalkyl group, an aralkyl group. Or an aryl group.

The alkyl group is preferably one having 1 to carbon atoms.
10 alkyl groups are preferred, for example, methyl, ethyl, propyl (and its isomers), butyl (and its isomers), pentyl (and its isomers), hexyl (and its isomers) , A heptyl group (and its isomers), an octyl group (and its isomers), a nonyl group (and its isomers), and a decyl group (and its isomers).

The cycloalkyl group is particularly preferably an alkenyl group having 3 to 7 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and a cycloheptyl group.

The aralkyl group preferably has 7 carbon atoms.
The aralkyl group of 10 to 10 is preferable, and examples thereof include a benzyl group, a phenethyl group (and its isomer), a phenylpropyl group (and its isomer), and a phenylbutyl group (and its isomer).

The aryl group is preferably a compound having 6 to 6 carbon atoms.
Preferred are 14 aryl groups, for example, a phenyl group, a naphthyl group, and an anthranyl group.

R ¹ , R ² and R ³ may be bonded to each other to form a ring, or the ring may contain a hetero atom.

The above-mentioned alkyl group, cycloalkyl group, aralkyl group and aryl group may have a substituent. Examples of the substituent include a substituent formed through a carbon atom, a substituent formed through an oxygen atom, a substituent formed through a nitrogen atom, and at least one substituent selected from a halogen atom.

Examples of the substituent formed through the carbon atom include an alkyl group such as a methyl group, an ethyl group, a propyl group and a butyl group; an aralkyl group such as a benzyl group; an alkenyl group such as an ethenyl group; and an alkynyl group such as an ethynyl group. Groups; aryl groups such as phenyl groups; cyano groups; carboxyl groups

Examples of the substituent formed through the oxygen atom include an alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, a butoxy group and a benzyloxy group; an aryloxy group such as a phenoxy group; an acetyloxy group and a benzoyloxy group. And the like.

The substituents formed via the nitrogen include:
A nitro group; an amino group.

As the halogen atom, a fluorine atom,
Examples include a chlorine atom, a bromine atom and an iodine atom.

In the general formula (1), R ⁴ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group which may have a substituent.

The alkyl group is preferably a compound having 1 to 1 carbon atoms.
10 alkyl groups are preferred, for example, methyl, ethyl, propyl (and its isomers), butyl (and its isomers), pentyl (and its isomers), hexyl (and its isomers) , A heptyl group (and its isomers), an octyl group (and its isomers), a nonyl group (and its isomers), and a decyl group (and its isomers).

The cycloalkyl group is particularly preferably an alkenyl group having 3 to 7 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and a cycloheptyl group.

The aralkyl group preferably has 7 carbon atoms.
The aralkyl group of 10 to 10 is preferable, and examples thereof include a benzyl group, a phenethyl group (and its isomer), a phenylpropyl group (and its isomer), and a phenylbutyl group (and its isomer).

The aryl group is preferably a compound having 6 to 6 carbon atoms.
Preferred are 14 aryl groups, for example, a phenyl group, a naphthyl group, and an anthranyl group.

The above-mentioned alkyl group, cycloalkyl group, aralkyl group or aryl group may have a substituent. Examples of the substituent include a substituent formed through a carbon atom, a substituent formed through an oxygen atom, a substituent formed through a nitrogen atom, and at least one substituent selected from a halogen atom.

The substituents formed through the carbon atom include alkyl groups such as methyl group, ethyl group, propyl group and butyl group; aralkyl groups such as benzyl group; alkenyl groups such as ethenyl group; alkynyl groups such as ethynyl group. Groups; aryl groups such as phenyl groups; cyano groups; carboxyl groups

Examples of the substituent formed through the oxygen atom include an alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, a butoxy group and a benzyloxy group; an aryloxy group such as a phenoxy group; an acetyloxy group and a benzoyloxy group. And the like.

Examples of the substituent formed through the nitrogen include:
A nitro group; an amino group.

As the halogen atom, a fluorine atom,
Examples include a chlorine atom, a bromine atom and an iodine atom.

The base used in the present invention is an inorganic base or an organic base. Examples of the inorganic base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide;
Alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal phosphates such as sodium phosphate, disodium hydrogen phosphate, potassium phosphate and dipotassium hydrogen phosphate; sodium acetate, potassium acetate, sodium propionate, propion Alkali metal organic acid salts such as potassium acid; and alkali metal alkoxides such as sodium methoxide and potassium methoxide. Preferred are alkali metal hydroxides, and more preferably sodium hydroxide.

Examples of the organic base include trimethylamine, triethylamine, ethyldiisopropylamine,
Tertiary amines such as diethylisopropylamine, triisopropylamine, benzyldimethylamine, and benzyldiethylamine; pyridines such as pyridine, methylpyridine, and dimethylpyridine are exemplified, but amines are more preferred, and triethylamine is more preferably used. .

The amount of the base to be used is preferably 0.1 to 5.0 times, more preferably 0.2 to 2.5 times, the mol of the starting β-ketoester. These bases may be used alone or in combination of two or more.

The hydrogen peroxide used in the reaction of the present invention is preferably an aqueous solution, and its concentration is preferably
It is 5 to 70% by weight, more preferably 30 to 50% by weight.
The amount used is based on the raw material β-ketoester.
Preferably it is 0.1 to 3.0 times mol, more preferably 0.2 to 2.5 times mol.

The reaction of the present invention is preferably performed in the presence of a solvent. The solvent to be used is not particularly limited as long as the reaction system can be made uniform, and examples thereof include alcohols such as methanol, ethanol, isopropyl alcohol, and t-butyl alcohol; and water.

The amount of the solvent to be used is preferably 0 to 50 ml, more preferably 0 to 50 ml, per 1 g of the raw material β-ketoester.
~ 30ml. These solvents may be used alone or in combination of two or more.

In the reaction of the present invention, the β-ketoester and hydrogen peroxide are preferably brought into contact in a liquid phase in the presence of a base. For example, after the β-ketoester and the solvent are mixed in an inert gas atmosphere, , Hydrogen peroxide and a base are added dropwise, and the mixture is heated and stirred at normal pressure or under pressure. The reaction temperature at that time is preferably 10 to 90 ° C,
More preferably, it is 20 to 60 ° C.

The obtained product (ketone) is separated and purified by a general method such as column chromatography, distillation and recrystallization after treating the remaining hydrogen peroxide after the reaction with a reducing agent. You.

[0048]

EXAMPLES Next, the present invention will be described specifically with reference to examples, but the scope of the present invention is not limited to these examples.

Example 1 0.456 g (2.1 mmol) of ethyl 2-benzyl-3-oxobutanoate and 5 ml of methanol were added to a 10 ml glass flask equipped with a dropping funnel, a stirrer, a thermometer and a reflux condenser. The temperature was raised to 40 ° C. while stirring. Then 35% by weight
A mixture of 0.400 g (4.1 mmol) of aqueous hydrogen peroxide and 0.18 ml (1.4 mmol) of an 8N aqueous sodium hydroxide solution was slowly added dropwise.
Thereafter, the reaction was carried out at the same temperature for 4 hours. After the completion of the reaction, the obtained reaction solution was analyzed by high performance liquid chromatography to find that 0.120 g (yield 38%) of benzylacetone was produced.

Example 2 Into the same reactor as in Example 1, 0.292 g (2.0 mmol) of methyl 5-methyl-3-oxohexanoate and 5 ml of methanol were added, and the temperature was raised to 40 ° C. with stirring. Then 35% by weight
0.390 g (4.0 mmol) of hydrogen peroxide and 0.410 of triethylamine
g (4.1 mmol) was slowly added dropwise. Then 50
The temperature was raised to 0 ° C., and the reaction was performed for 2 hours. After the completion of the reaction, the obtained reaction solution was analyzed by high performance liquid chromatography to find that 0.078 g (yield: 45%) of methyl isopropyl ketone was produced.

Example 3 Into the same reactor as in Example 1, 0.356 g (2.0 mmol) of methyl α-benzoylacetate and 5 ml of methanol were added, and the temperature was raised to 40 ° C. with stirring. Then, 35% by weight hydrogen peroxide solution
A mixture of 0.390 g (4.0 mmol) and 0.410 g (4.2 mmol) of triethylamine was slowly added dropwise. Thereafter, the temperature was raised to 50 ° C., and the reaction was performed for 2 hours. After completion of the reaction, the obtained reaction solution was analyzed by high performance liquid chromatography to find that 0.113 g (yield 47%) of acetophenone was produced.

Example 4 To a reaction apparatus similar to that of Example 1, 0.456 g (2.1 mmol) of ethyl 2-benzyl-3-oxobutanoate and 5 ml of methanol were added, and the temperature was raised to 40 ° C. with stirring. Then 35% by weight
0.390 g (4.0 mmol) of hydrogen peroxide and 0.410 of triethylamine
g (4.2 mmol) was slowly added dropwise. Then 50
The temperature was raised to 0 ° C., and the reaction was performed for 2 hours. After the completion of the reaction, the obtained reaction solution was analyzed by high performance liquid chromatography to find that 0.258 g (yield 83%) of benzylacetone was produced.

Reference Example 1 Synthesis of 1-acetyl-1-carbomethoxycyclopentane A compound was synthesized according to the method described in J. Org. Chem., 61 , 73 (1996). In a 500 ml glass flask equipped with a dropping funnel, a stirrer, a thermometer and a reflux condenser, 59.0 ml (0.5 mol) of 1,4-dibromobutane, 82.9 g of anhydrous potassium carbonate (0.6 mol
l), 8.3 g (0.05 mol) of potassium iodide and 200 ml of dimethylformamide were added, and the temperature was raised to 80 ° C. while stirring.
Then, 64.8 ml (0.6 mol) of methyl 3-oxobutanoate was slowly added dropwise. Thereafter, the reaction was carried out at the same temperature for 5 hours.
After completion of the reaction, 500 ml of water was added to the obtained reaction solution, and the mixture was extracted three times with 200 ml of ethyl acetate. Then, after separating the organic layer, the residue was distilled under reduced pressure (40-60 ° C, 5-10 mmHg) to give 1-acetyl-1-carbomethoxycyclopentane having a purity of 91% (area percentage by gas chromatography) as a pale yellow liquid. 1
7.0 g were obtained (20% yield). Physical properties of 1-acetyl-1-carbomethoxycyclopentane were determined by CI-MS (m / e); 171 (M + 1), ¹ H
-NMR (CDCl ₃ ); 1.60 ppm (4H, m), 2.10 ppm (4H, m), 2.17 ppm
(3H, s) and 3.72 ppm (3H, s).

Example 5 A 91% pure 1-acetyl-1-carbomethoxycyclo synthesized in Reference Example 1 was placed in a 100-ml glass flask equipped with a dropping funnel, a stirrer, a thermometer, and a reflux condenser. 1.59 g (8.5 mmol) of pentane and 50 ml of methanol were added, and the temperature was raised to 40 ° C. with stirring. Then, 35% by weight hydrogen peroxide solution
A mixture of 1.65 g (17 mmol) and 1.72 g (17 mmol) of triethylamine was slowly added dropwise. Then, raise the temperature to 50 ° C
Allowed to react for hours. After completion of the reaction, 5 ml of a saturated aqueous sodium sulfite solution was added to the obtained reaction solution to treat the remaining hydrogen peroxide, and then methanol was distilled off under reduced pressure. Thereafter, the mixture was extracted three times with 30 ml of ethyl acetate, and then the organic layer was separated and concentrated under reduced pressure to obtain a light yellow liquid having a purity of 82%.
0.83 g of cyclopentyl methyl ketone (% by area by gas chromatography) was obtained (yield: 71%). Physical properties of cyclopentyl methyl ketone are CI-MS (m / e); 113
(M + 1), ¹ H-NMR (CDCl ₃ ); 1.67 ppm (8H, m), 2.10 ppm (3H,
m), 2.6 to 3.1 ppm (1H, m) and 3.72 ppm (3H, s).

[0055]

According to the present invention, from β-ketoester,
It is possible to provide an industrially suitable method for producing a ketone, which can produce a ketone in a high yield under a mild condition without a complicated operation.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Minoru Nishimura 5 in 1978 Kogushi, Oji, Ube City, Yamaguchi Prefecture Inside Ube Research Laboratories Co., Ltd. F-term in Ube Laboratory Co., Ltd. (reference) 4H006 AA02 AC22 AC44 BE32

Claims (1)

[Claims] 1. A compound of the formula (1) in the presence of a base (Wherein, R ¹ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group which may have a substituent. R ² and R ³ may be the same or different;
It represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group which may have a substituent.
R ¹ , R ² and R ³ may be bonded to each other to form a ring, or may contain a hetero atom in the ring.
R ⁴ represents an optionally substituted alkyl group, cycloalkyl group, aralkyl group or aryl group. Wherein the β-ketoester represented by the formula) is reacted with hydrogen peroxide. (Wherein R ¹ , R ² and R ³ are as defined above).